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Published on: October 12, 2013
Cytokine-mediated PGE2 expression in human colonic fibroblasts
1Division of Gastroenterology, Department of Medicine, Veterans Affairs Medical Center and Buffalo General Hospital, State University of New York, Buffalo 14215, USA.
The American Journal of Physiology
|October 1, 1998
Summary
Human colonic fibroblasts are key targets for cytokines, significantly increasing prostaglandin E2 (PGE2) production. These fibroblasts also respond to PGE2, influencing their morphology and suggesting a vital role in the colon.
Area of Science:
- Gastroenterology
- Cell Biology
- Immunology
Background:
- Prostanoids, like PGE2, play crucial roles in colonic homeostasis and inflammation.
- Understanding the cellular sources and regulation of PGE2 in the colon is essential for therapeutic development.
Purpose of the Study:
- To investigate prostanoid biogenesis in human colonic fibroblasts and epithelial cells.
- To determine the effect of PGE2 on fibroblast morphology.
- To evaluate cytokine-induced PGE2 production and its regulatory mechanisms.
Main Methods:
- Cultured human colonic fibroblast and epithelial cell lines (CCD-18Co, NCM460, T84, HT-29, LS 174T, and primary fibroblasts).
- Measurement of prostaglandin E2 (PGE2) production via ELISA.
- Assessment of prostaglandin H synthase-1 and -2 (PGHS-1 and -2) protein and mRNA expression using Western blot and RT-PCR.
- Evaluation of PGE2 effects on fibroblast morphology.
Main Results:
- Basal PGE2 levels were low across all cell types.
- Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) significantly induced PGE2 synthesis in colonic fibroblasts (up to 25-fold), with minimal induction in epithelial cells.
- IL-1beta upregulated PGHS-2 protein and mRNA in fibroblasts but not PGHS-1.
- PGE2 treatment altered fibroblast morphology.
Conclusions:
- Colonic fibroblasts are potent producers of PGE2 in response to inflammatory cytokines.
- Fibroblast-derived PGE2 may influence colonic tissue through morphological changes.
- Colonic fibroblasts are significant cytokine targets and play a role in colonic prostanoid signaling in vivo.
